Document Detail


Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease.
MedLine Citation:
PMID:  16690904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4-5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.
Authors:
Dariusz Stepniak; Liesbeth Spaenij-Dekking; Cristina Mitea; Martine Moester; Arnoud de Ru; Renee Baak-Pablo; Peter van Veelen; Luppo Edens; Frits Koning
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-11
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  291     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-08     Completed Date:  2006-10-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G621-9     Citation Subset:  IM    
Affiliation:
Dept. of Immunohematology and Blood Transfusion, Leiden Univ. Medical Center, P.O. BOX 9600, 2300 RC Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Aspergillus niger / enzymology*
Celiac Disease / enzymology*
Enzyme Stability
Flavobacterium / enzymology
Glutens / metabolism*
Humans
Hydrogen-Ion Concentration
Pepsin A
Serine Endopeptidases / metabolism*
Stomach
T-Lymphocytes / metabolism
Trypsin
Chemical
Reg. No./Substance:
8002-80-0/Glutens; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.26/prolyl oligopeptidase; EC 3.4.21.4/Trypsin; EC 3.4.23.1/Pepsin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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